This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Abstract Using Molecular Dynamic (MD) simulations, computational protein modification, and Thermodynamic Integration (TI) method we will concentrate on the studying of the PDZ-ligand complexes of Na/H Exchange Regulatory Factor-1 (NHERF1) due to their biological and medicinal importance. We will investigate the PDZ2-ligand interactions. To probe such interactions we will use the five amino acid residue motifs WETVM (L1) or LFSNL (L2). We are planning to estimate binding affinity of PDZ2 for both L1 and L2.